ArticleNeuroImage2016
The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.
Article in NeuroImage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
- Alzheimer's disease-like brain pattern biomarker: capturing risks and predicting disease onset.Molecular psychiatry · 2026Article
- Cerebral Blood Flow Responses to Extracranial Alternating Current Brain Stimulation in CVN Mouse Model of Alzheimer's Disease: A Pilot Study Determining Optimal Dose.Neuromodulation : journal of the International Neuromodulation Society · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.Frontiers in neuroscience · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: Implications for translational validity to the human.bioRxiv : the preprint server for biology · 2025Article
- Alzheimer's Disease-Like Brain Pattern Biomarker: Capturing Risks and Predicting Disease Onset.Research square · 2025Article
- Neuroimaging biomarkers of neuroprotection: Impact of voluntary versus enforced exercise in Alzheimer's disease models.Magnetic resonance imaging · 2025Article
- Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Temporal Alterations in White Matter in AneNeuro · 2024Article
- The genetic architecture of fornix white matter microstructure and their involvement in neuropsychiatric disorders.Translational psychiatry · 2023Article
- Infection and inflammation: New perspectives on Alzheimer's disease.Brain, behavior, & immunity - health · 2022Review
- Neuroimaging of Mouse Models of Alzheimer's Disease.Biomedicines · 2022Review
- Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging.Frontiers in neuroscience · 2022Article
- Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory.Frontiers in behavioral neuroscience · 2022Article
- Magnetic Resonance Imaging in Animal Models of Alzheimer's Disease Amyloidosis.International journal of molecular sciences · 2021Review
- Diffusion MRI detects basal forebrain cholinergic abnormalities in the 3xTg-AD mouse model of Alzheimer's disease.Magnetic resonance imaging · 2021Article
- 1700 nm optical coherence microscopy enables minimally invasive, label-free, in vivo optical biopsy deep in the mouse brain.Light, science & applications · 2021Article
- Contrasting Metabolic Insufficiency in Aging and Dementia.Aging and disease · 2021Review
- Article
- Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.Magnetic resonance imaging · 2021Article
- A White Matter Connection of Schizophrenia and Alzheimer's Disease.Schizophrenia bulletin · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination-through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.